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目的研究射线诱导下Egr-1基因启动子调控腺病毒介导的Smad 7基因在C57BL/6J小鼠Lewis肺癌原发病灶内表达后,对原发灶及远处肺转移发生的影响。方法将Egr-1基因启动子的辐射敏感元件和Smad 7 cDNA包装到复制缺陷型腺病毒内,制备成AD.Egr-Smad 7。接种Lewis肺癌细胞于小鼠右后肢外侧,建立荷瘤小鼠模型,肿瘤直径达0.8~1.0 cm时进行实验。小鼠被随机分入空白对照、生理盐水(NS)对照、AD.Egr-Smad 7对照、单纯照射、NS+照射、AD.Egr-Smad 7+照射组(6只/组),分别进行如下研究:(1)隔日记录肿瘤长径及短径,观察肿瘤生长曲线、生长延迟时间及小鼠生存时间;(2)观察肿瘤照射2周时肺转移发生情况;(3)观察肿瘤生长至照射时4倍体积时肺转移发生情况。结果放射线诱导Egr-1基因启动子调控腺病毒介导的Smad 7基因在C57BL小鼠Lewis肺癌原发病灶内表达后,有抑制原发肿瘤生长及延长小鼠生存时间的作用(P<0.05),对肿瘤远处肺转移的发生无明显影响(P>0.05)。结论放射线诱导AD.Egr-Smad 7无促进小鼠Lewis肺癌肿瘤局部病灶发展及远处脏器转移的危险性,并且有抑制原发肿瘤生长及延长生存时间的作用。将AD.Egr-Smad 7用于阻断TGF-β信号传导通路,靶向性基因治疗放射性肺纤维化具有一定的安全性。
Objective To investigate the effect of Egr-1 gene promoter on the metastasis of primary lung cancer and lung in Lewis lung carcinoma of C57BL / 6J mice after radiation-induced expression of adenovirus-mediated Smad 7 gene. Methods The radiation-sensitive element of Egr-1 gene promoter and Smad 7 cDNA were packaged into replication-deficient adenovirus to prepare AD.Egr-Smad 7. Lewis lung carcinoma cells were inoculated to the outside of the right hind limbs of mice and a tumor-bearing mouse model was established. Experiments were performed when the tumor diameter reached 0.8-1.0 cm. The mice were randomized into blank control, saline (NS) control, AD.Egr-Smad 7 control, simple irradiation, NS + irradiation and AD.Egr-Smad 7+ irradiation group (6 mice / group) (2) observe the occurrence of lung metastasis 2 weeks after tumor irradiation; (3) observe the growth of tumor to irradiation 4 times the volume of lung metastasis occurs. Results Radiation-induced Egr-1 gene promoter regulation of adenovirus-mediated Smad 7 gene expression in primary lung cancer Lewis lung carcinoma C57BL mice, the inhibition of primary tumor growth and prolong survival of mice (P <0.05) , No significant effect on distant lung metastasis (P> 0.05). Conclusion Radiation-induced AD.Egr-Smad 7 can not promote the development of local lesions and metastasis of distant organs in mice with Lewis lung cancer, and can inhibit the growth of primary tumors and prolong the survival time. AD.Egr-Smad 7 is used to block the TGF-β signaling pathway, targeted gene therapy for radiation-induced pulmonary fibrosis has some safety.